T cells derived from umbilical cord blood

Abstract

Methods for producing therapeutic T cells from umbilical cord blood are provided. Methods for treating immune-related diseases or conditions (e.g. autoimmune diseases, transplant rejection, cancer) using umbilical cord blood derived therapeutic T cells are also provided. Compositions comprising umbilical cord blood derived therapeutic T cells are also provided.

The invention claimed is: 
     
       1. An inducible regulatory T cell composition comprising an expanded iTreg composition produced by a method comprising:
 providing human umbilical cord blood; 
 isolating naïve CD4 +  T cells from the human umbilical cord blood; 
 inducing the naïve CD4 +  T cells to differentiate into a first composition comprising iTregs by treating the naïve CD4 +  T cells with TGF-β; 
 separating the iTregs from the first composition to form a substantially purified iTreg composition; and 
 expanding the purified iTreg composition in a composition comprising a mesenchymal stromal cell (MSC) feeder layer and IL-2 to form an expanded human iTreg composition expressing CD4 + , CD25 + , CD45RA +  and Foxp3 +  proteins at higher levels than iTregs not expanded over a MSC feeder cell layer. 
 
     
     
       2. A therapeutic regulatory T cell composition comprising a therapeutically effective dose of human umbilical cord blood derived iTregs expanded in a composition comprising mesenchymal stromal cells and IL-2. 
     
     
       3. A therapeutic composition comprising a therapeutic T cell composition made by a method comprising:
 providing human umbilical cord blood; 
 isolating naïve CD4 +  T cells from the umbilical cord blood; and 
 manufacturing a therapeutic T cell composition comprising iTregs from the isolated naïve CD4 +  T cells, wherein the manufacturing comprises expanding the iTregs in a composition comprising a mesenchymal stromal cell (MSC) feeder layer and IL-2. 
 
     
     
       4. The inducible regulatory T cell composition of  claim 1 , wherein the iTregs are separated from the first composition using flow cytometry cell sorting or magnetic cell sorting. 
     
     
       5. The inducible regulatory T cell composition of  claim 1 , wherein the purified iTreg composition is at least 90% pure. 
     
     
       6. The therapeutic regulatory T cell composition of  claim 2 , wherein the expanded human iTregs express CD4+, CD25+, CD45RA+ and Foxp3+ proteins at higher levels than iTregs not expanded over a MSC feeder layer. 
     
     
       7. The therapeutic composition of  claim 3 , wherein the T cell composition comprises expanded human iTregs expressing CD4+, CD25+, CD45RA+ and Foxp3+ proteins at higher levels than iTregs not expanded over a MSC feeder layer. 
     
     
       8. The inducible regulatory T cell composition of  claim 1 , wherein the expanded human iTreg composition expresses CTLA4, CD25, and Foxp3 at higher levels compared to iTregs prepared from CD4 +  T cells derived from adult blood. 
     
     
       9. The inducible regulatory T cell composition of  claim 1 , wherein the expanded human iTreg composition has an enhanced ability to modulate dendritic cells compared to iTregs prepared from CD4 +  T cells derived from adult blood. 
     
     
       10. The inducible regulatory T cell composition of  claim 1 , wherein the expanded human iTreg composition has an enhanced stability of Foxp3 expression compared to iTregs prepared from CD4 +  T cells derived from adult blood. 
     
     
       11. The inducible regulatory T cell composition of  claim 1 , wherein the expanded human iTreg composition has an enhanced suppressive activity compared to iTregs prepared from CD4 +  T cells derived from adult blood. 
     
     
       12. The therapeutic regulatory T cell composition of  claim 1 , wherein the human umbilical cord blood derived iTregs express CTLA4, CD25, and Foxp3 at higher levels compared to adult blood derived iTregs. 
     
     
       13. The therapeutic regulatory T cell composition of  claim 1 , wherein the human umbilical cord blood derived iTregs have an enhanced stability of Foxp3 expression compared to iTregs prepared from CD4 +  T cells derived from adult blood. 
     
     
       14. The therapeutic composition of  claim 3 , wherein the iTregs manufactured from the naïve CD4 +  T cells isolated from the umbilical cord blood express CTLA4, CD25, and Foxp3 at higher levels compared to iTregs manufactured from naïve CD4 +  T cells isolated from adult blood. 
     
     
       15. The therapeutic composition of  claim 3 , wherein the iTregs manufactured from the naïve CD4 +  T cells isolated from the umbilical cord blood have an enhanced stability of Foxp3 expression compared to iTregs manufactured from naïve CD4 +  T cells isolated from adult blood. 
     
     
       16. The inducible regulatory T cell composition of  claim 1 , wherein the inducing and expanding steps are performed without rapamycin. 
     
     
       17. The inducible regulatory T cell composition of  claim 1 , wherein the MSC feeder layer is derived from a healthy subject.